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David R Snydman

Publications and source records attributed to David R Snydman.

33 records · Page 2Linked to original sources

Emergence of fluoroquinolone resistance among Bacteroides species.

BACKGROUND: Several newer generation fluoroquinolones have demonstrated good in vitro activity against Bacteroides species; particularly when first introduced. However, resistance of Bacteroides to quinolones appears to be increasing. MATERIALS AND METHODS: From 1994 to 2001, consecutive non-duplicated Bacteroides isolates from clinical specimens in 12 US hospitals were sent to the Tufts anaerobe laboratory for identification and susceptibility testing. NCCLS recommended methodology for testing was employed. Breakpoints of 8 mg/l for trovafloxacin and 4 mg/l for moxifloxacin were used to examine susceptibility trends. RESULTS: In total, 4434 isolates were analysed. The geometric mean MIC increased significantly for clinafloxacin, trovafloxacin and moxifloxacin. Resistance to trovafloxacin (breakpoint of 8 mg/l) and moxifloxacin (breakpoint of 4 mg/l) increased from 8% to 25% and from 30% to 43%, respectively. Increased resistance was observed for all Bacteroides species, for all sites of isolation, and in 11 of 12 participating hospitals. Bacteroides vulgatus and isolates from decubitus ulcers were associated with increased resistance. During 2001, trovafloxacin and moxifloxacin resistance among blood isolates was 27% and 52%, respectively. The association between increased resistance and year of isolation remained significant after adjustment for hospital, species and site of isolation. CONCLUSIONS: Fluoroquinolone resistance among Bacteroides isolated in the US has markedly increased during the years 1994 to 2001. High rates of resistance among blood isolates are of particular concern.

Academic Medical Centers↗

An international prospective study of pneumococcal bacteremia: correlation with in vitro resistance, antibiotics administered, and clinical outcome.

We performed a prospective, international, observational study of 844 hospitalized patients with blood cultures positive for Streptococcus pneumoniae. Fifteen percent of isolates had in vitro intermediate susceptibility to penicillin (minimum inhibitory concentration [MIC], 0.12-1 microg/mL), and 9.6% of isolates were resistant (MIC, >or=2 microg/mL). Age, severity of illness, and underlying disease with immunosuppression were significantly associated with mortality; penicillin resistance was not a risk factor for mortality. The impact of concordant antibiotic therapy (i.e., receipt of a single antibiotic with in vitro activity against S. pneumoniae) versus discordant therapy (inactive in vitro) on mortality was assessed at 14 days. Discordant therapy with penicillins, cefotaxime, and ceftriaxone (but not cefuroxime) did not result in a higher mortality rate. Similarly, time required for defervescence and frequency of suppurative complications were not associated with concordance of beta-lactam antibiotic therapy. beta-Lactam antibiotics should still be useful for treatment of pneumococcal infections that do not involve cerebrospinal fluid, regardless of in vitro susceptibility, as determined by current NCCLS breakpoints.

Adolescent↗

Severe sepsis: variation in resource and therapeutic modality use among academic centers.

BACKGROUND: Treatment of severe sepsis is expensive, often encompassing a number of discretionary modalities. The objective of the present study was to assess intercenter variation in resource and therapeutic modality use in patients with severe sepsis. METHODS: We conducted a prospective cohort study of 1028 adult admissions with severe sepsis from a stratified random sample of patients admitted to eight academic tertiary care centers. The main outcome measures were length of stay (LOS; total LOS and LOS after onset of severe sepsis) and total hospital charges. RESULTS: The adjusted mean total hospital charges varied from 69 429 dollars to US237 898 dollars across centers, whereas the adjusted LOS after onset varied from 15.9 days to 24.2 days per admission. Treatments used frequently after the first onset of sepsis among patients with severe sepsis were pulmonary artery catheters (19.4%), ventilator support (21.8%), pressor support (45.8%) and albumin infusion (14.4%). Pulmonary artery catheter use, ventilator support and albumin infusion had moderate variation profiles, varying 3.2-fold to 4.9-fold, whereas the rate of pressor support varied only 1.92-fold across centers. Even after adjusting for age, sex, Charlson comorbidity score, discharge diagnosis-relative group weight, organ dysfunction and service at onset, the odds for using these therapeutic modalities still varied significantly across centers. Failure to start antibiotics within 24 hours was strongly correlated with a higher probability of 28-day mortality (r2 = 0.72). CONCLUSION: These data demonstrate moderate but significant variation in resource use and use of technologies in treatment of severe sepsis among academic centers. Delay in antibiotic therapy was associated with worse outcome at the center level.

Academic Medical Centers↗

Randomized comparison of oral valacyclovir and intravenous ganciclovir for prevention of cytomegalovirus disease after allogeneic bone marrow transplantation.

In this multicenter, randomized study, cytomegalovirus (CMV)-seropositive patients who received an allogeneic bone marrow transplant were provided high-dose intravenous acyclovir (500 mg/m(2) q8h) from the day of transplantation until engraftment. The patients were then randomly assigned to receive either oral valacyclovir, 2 g q.i.d. (n=83), or intravenous ganciclovir, 5 mg/kg q12h for 1 week, then 6 mg/kg once daily for 5 days per week (n=85), until day 100 after transplantation. CMV infection occurred in 12% of the patients who received valacyclovir and in 19% of the patients who received ganciclovir (hazard ratio [HR], 1.042; 95% confidence interval [CI], 0.391-2.778; P=.934). CMV disease developed in only 2 patients who received valacyclovir and in 1 patient who received ganciclovir (HR, 1.943; 95% CI, 0.176-21.44; P=.588). Oral valacyclovir can be an effective alternative to intravenous ganciclovir for prophylaxis of CMV disease after bone marrow transplantation.

Acyclovir↗

Resource utilization among patients with sepsis syndrome.

OBJECTIVE: To assess the resource utilization associated with sepsis syndrome in academic medical centers. DESIGN: Prospective cohort study. SETTING: Eight academic, tertiary-care centers. PATIENTS: Stratified random sample of 1,028 adult admissions with sepsis syndrome and all 248,761 other adult admissions between January 1993 and April 1994. The main outcome measures were length of stay (LOS) in total and after onset of sepsis syndrome (post-onset LOS) and total hospital charges. RESULTS: The mean LOS for patients with sepsis was 27.7 +/- 0.9 days (median, 20 days), with sepsis onset occurring after a mean of 8.1 +/- 0.4 days (median, 3 days). For all patients without sepsis, the LOS was 7.2 +/- 0.03 days (median, 4 days). In multiple linear regression models, the mean for patients with sepsis syndrome was 18.2 days, which was 11.0 days longer than the mean for all other patients (P < .0001), whereas the mean difference in total charges was $43,000 (both P < .0001). These differences were greater for patients with nosocomial as compared with community-acquired sepsis, although the groups were similar after adjusting for pre-onset LOS. Eight independent correlates of increased post-onset LOS and 12 correlates of total charges were identified. CONCLUSIONS: These data quantify the resource utilization associated with sepsis syndrome, and demonstrate that resource utilization is high in this group. Additional investigation is required to determine how much of the excess post-onset LOS and charges are attributable to sepsis syndrome rather than the underlying medical conditions.

Academic Medical Centers↗

Relationship of pulmonary artery catheter use to mortality and resource utilization in patients with severe sepsis.

OBJECTIVE: To examine the relationship of pulmonary artery catheter (PAC) use to patient outcomes, including mortality rate and resource utilization, in patients with severe sepsis in eight academic medical centers. DESIGN: Case-control, nested within a prospective cohort study. SETTING: Eight academic tertiary care centers. PATIENTS: Stratified random sample of 1,010 adult admissions with severe sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcome measures were in-hospital mortality, total hospital charge, and length of stay (LOS) for patients with and without PAC use. The case-matched subset of patients included 141 pairs managed with and without the use of a PAC. The mortality rate was slightly but not statistically significantly lower among the PAC use group compared with those not using a PAC (41.1% vs. 46.8%, p =.34). Even this trend disappeared after we adjusted for the Charlson comorbidity score and sepsis-specific Acute Physiology and Chronic Health Evaluation (APACHE) III (adjusted odds ratio, 1.02; 95% confidence interval, 0.61-1.72). In linear regression models adjusted for the Charlson comorbidity score, sepsis-specific APACHE III, surgical status, receipt of a steroid before sepsis onset, presence of a Hickman catheter, and preonset LOS, no significant differences were found for total hospital charges (139,207 US dollars vs. 148,190, adjusted mean comparing PAC and non-PAC group, p =.57), postonset LOS (23.4 vs. 26.9 days, adjusted mean, p =.32), or total LOS in intensive care unit (18.2 vs. 18.8 days, adjusted mean, p =.82). CONCLUSIONS: Among patients with severe sepsis, PAC placement was not associated with a change in mortality rate or resource utilization, although small nonsignificant trends toward lower resource utilization were present in the PAC group.

APACHE↗

Shifting patterns in the epidemiology of nosocomial Candida infections.

The incidence of candidemia--a common and potentially fatal nosocomial infection--has risen dramatically, and this increase has been accompanied by a shift in the infecting pathogen away from Candida albicans to treatment-resistant non-albicans species. Prophylactic azole antifungals, such as fluconazole, may play an important role not only in the management of candidemia but also in the proliferation of hard-to-treat Candida species. In a variety of acute nosocomial settings, IV fluconazole, 400 mg/d, has reduced Candida colonization and infection. A growing body of evidence supports the still controversial contention that the increasing use of azole antifungals is at least partially responsible for the proliferation of treatment-resistant, non-albicans isolates, especially Candida glabrata. Thus, selecting the most appropriate candidates for prophylactic antifungal intervention--ie, those with the highest risk for candidemia--may be indispensable, not only in preventing candidemia, but also in reducing antifungal overuse, which may contribute to the emergence of treatment-resistant Candida isolates.

Antifungal Agents↗

Association between the presence of enterococcal virulence factors gelatinase, hemolysin, and enterococcal surface protein and mortality among patients with bacteremia due to Enterococcus faecalis.

The potential virulence factors of enterococci include production of enterococcal surface protein (Esp), gelatinase, and hemolysin. Gelatinase- and hemolysin-producing strains of Enterococcus faecalis have been shown to be virulent in animal models of enterococcal infections. Esp production has been shown to enhance the persistence of E. faecalis in the urinary bladder. We determined the presence of the esp gene and production of gelatinase and hemolysin in 219 E. faecalis isolates from a larger prospective study of 398 patients with enterococcal bacteremia. Thirty-two percent of isolates carried the esp gene, 64% produced gelatinase, and 11% produced hemolysin. There was no significant association between 14-day mortality and any of the markers studied, singly or in combination.

Adolescent↗

Attributable mortality of Stenotrophomonas maltophilia bacteremia.

A systematic evaluation of the attributable mortality of Stenotrophomonas maltophilia bacteremia was undertaken in a matched, retrospective, case-control study. We determined the attributable mortality rate (26.7%) and mortality risk ratio (an 8-fold increase) of S. maltophilia bacteremia. The attributable mortality rate for S. maltophilia bacteremia is similar to the attributable mortality rate for other nosocomial bloodstream infections.

Bacteremia↗

Real-time antifungal susceptibility screening aids management of invasive yeast infections in immunocompromised patients.

We examined the utility of a semi-solid agar antifungal susceptibility screening (SAAS) test in real-time management of eight immunocompromised patients with invasive yeast infections. Tests of amphotericin B and fluconazole concentrations of 0.5 and 2 mg/L and 1, 8 and 40 mg/L, respectively, were performed on Candida albicans (two), Candida tropicalis (two), Candida krusei (one), Candida glabrata (one) and Trichosporon species (spp.) (two). All but the Trichosporon spp. and C. glabrata isolates were resistant to fluconazole at > or = 40 mg/L, and patients were successfully managed accordingly. Real-time antifungal susceptibility screening can assist in clinical management of invasive yeast infections.

Adult↗

Clinical utility of blood cultures drawn from central venous or arterial catheters in critically ill surgical patients.

OBJECTIVE: To determine the sensitivity, specificity, and predictive values of cultures done with blood drawn through a central venous or arterial catheter compared with peripheral venipuncture. DESIGN: Retrospective cohort study of critically ill surgical patients in whom samples for paired cultures were drawn through a central venous or arterial catheter and peripheral venipuncture. SETTING: Tertiary-care, university-affiliated medical center. PATIENTS: Two hundred seventy-one patients hospitalized on a surgical and a cardiothoracic intensive care unit between November 1994 and August 1997. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blinded assessments of culture results done by two physicians were used as the gold standard. Sensitivity, specificity, and positive and negative predictive values were compared for culture of blood from catheters and culture of blood from peripheral venipuncture. Of 499 observations, 426 were catheter-negative/venipuncture-negative, 19 were catheter-positive/venipuncture-positive, 18 were catheter-negative/venipuncture-positive, and 36 were catheter-positive/venipuncture-negative pairs. For catheter draws compared with peripheral venipuncture, sensitivity was 78% (confidence interval [CI], 65% to 90%) and 65% (CI, 50% to 79%) (p = .2), specificity was 95% (CI, 94% to 97%) and 98% (CI, 97% to 99%) (p = .002), positive predictive value was 63% (CI, 51% to 76%) and 78% (CI, 64% to 91%) (p = .1) and negative predictive value was 98% (CI, 96% to 99%) and 97% (CI, 95% to 98%) (p = .3). When central venous specimens as differentiated from arterial catheter specimens were compared with peripheral venipuncture, the difference between positive predictive values reached statistical significance (61% and 82%; p = .04). CONCLUSIONS: In critically ill surgical patients, cultures of blood drawn through a catheter are less specific than those obtained from a peripheral venipuncture. Both types of cultures have an excellent negative predictive value. Positive predictive value of cultures of blood drawn through a catheter is low and, when obtained from a central line, statistically less than from a peripheral venipuncture. Additional cultures seem to be necessary for the proper interpretation of a positive culture drawn through a catheter in critical care patients.

Aged↗

The case for cytomegalovirus prophylaxis in solid organ transplantation.

Cytomegalovirus prevention strategies have been debated for the past decade. This review argues in favour of the prophylaxis strategy. Clinical trials comparing prophylaxis to pre-emptive therapy have, thus far, had insufficient power to differentiate strategies, especially with regard to the indirect effects of CMV. From meta-analyses, prospective trials, observational studies, and case control studies, there is evidence that prophylaxis prevents cytomegalovirus infection and disease, reduces the indirect effects of cytomegalovirus, including organ rejection and transplant associated, all cause mortality as well as opportunistic infection, and even bacteremia as well as post transplant lymphoproliferative disease. Prophylaxis has also been shown to be cost effective. One must recognise that with the current prophylaxis regimens employed for 3 months post-transplantation, late onset cases of cytomegalovirus disease may occur. Cytomegalovirus replication monitoring may be necessary after cessation of prophylaxis, especially in the high risk cytomegalovirus seropositive donor to cytomegalovirus seronegative recipient. Future trials with longer periods of prophylaxis are being undertaken.

Antiviral Agents↗